Optofluidics:the interaction between light and flowing liquids in integrated devices

Optofluidics is a rising technology that combines microfluidics and optics.Its goal is to manipulate light and flowing liquids on the micro/nanoscale and exploiting their interaction in optofluidic chips.The fluid flow in the on-chip devices is reconfigurable,non-uniform and usually transports substances being analyzed,offering a new idea in the accurate manipulation of lights and biochemical samples.In this paper,we summarized the light modulation in heterogeneous media by unique fluid dynamic properties such as molecular diffusion,heat conduction,centrifugation effect,light-matter interaction and others.By understanding the novel phenomena due to the interaction of light and flowing liquids,quantities of tunable and reconfigurable optofluidic devices such as waveguides,lenses,and lasers are introduced.Those novel applications bring us firm conviction that optofluidics would provide better solutions to high-efficient and high-quality lab-on-chip systems in terms of biochemical analysis and environment monitoring.

Tumour mutational burden is overestimated by target cancer gene panels

Background:Tumour mutational burden(TMB)has emerged as a predictive marker for responsiveness to immune checkpoint inhibitors(ICI)in multiple tumour types.It can be calculated from somatic mutations detected from whole exome or targeted panel sequencing data.As mutations are unevenly distributed across the cancer genome,the clinical implications from TMB calculated using different genomic regions are not clear.Methods:Pan-cancer data of 10,179 samples were collected from The Cancer Genome Atlas cohort and 6,831 cancer patients with either ICI or non-ICI treatment outcomes were derived from published papers.TMB was calculated as the count of non-synonymous mutations and normalised by the size of genomic regions.Dirichlet method,linear regression and Poisson calibration models are used to unify TMB from different gene panels.Results:We found that panels based on cancer genes usually overestimate TMB compared to whole exome,potentially leading to misclassification of patients to receive ICI.The overestimation is caused by positive selection for mutations in cancer genes and cannot be completely addressed by the removal of mutational hotspots.We compared different approaches to address this discrepancy and developed a generalised statistical model capable of interconverting TMB derived from whole exome and different panel sequencing data,enabling TMB correction for patient stratification for ICI treatment.We show that in a cohort of lung cancer patients treated with ICI,when using a TMB cutoffof 10 mut/Mb,our corrected TMB outperforms the original panel-based TMB.Conclusion:Cancer gene-based panels usually overestimate TMB,and these findings will be valuable for unifying TMB calculations across cancer gene panels in clinical practice.

Risk SNP-induced lncRNA-SLCCl drives colorectal cancer through activating glycolysis signaling

Long non-coding RNAs(lncRNAs)play key roles in colorectal carcinogenesis.Here,we aimed to identify the risk SNP-induced lncRNAs and to investigate their roles in colorectal carcinogenesis.First,we identified rs6695584 as the causative SNP in 1 q41 locus.The A>G mutation of rs6695584 created a protein-binding motif of BATF,altered the enhancer activity,and subsequently activated IncSLCCl expression.Further validation in two independent CRC cohorts confirmed the upregulation of IncSLCCl in CRC tissues,and revealed that increased IncSLCCl expression was associated with poor survival in CRC patients.Mechanistically,lncRNA-SLCCl interacted with AHR and transcriptionally activated HK2 expression,the crucial enzyme in glucose metabolism,thereby driving the glycolysis pathway and accelerating CRC tumor growth.The functional assays revealed that IncSLCCl induced glycolysis activation and tumor growth in CRC mediated by HK2.In addition,HK2 was upregulated in colorectal cancer tissues and positively correlated with IncSLCCl expression and patient survival.Taken together,our findings reveal a risk SNP-mediated oncogene lncRNA-SLCCl promotes CRC through activating the glycolysis pathway.

Long-term exposure to titanium dioxide nanoparticles promotes diet-induced obesity through exacerbating intestinal mucus layer damage and microbiota dysbiosis

Titanium dioxide nanoparticles (TiO2-NPs) are commonly used as food additives, including some high-fat foods that are risk factors for obesity. However, little is known about the effects of chronic TiO2-NPs digestion in the population on high fat diet (HFD). Herein, we reported that TiO2-NPs exacerbated HFD-induced obesity by disruption of mucus layer and alterations of gut microbiota. Oral intake of TiO2-NPs significantly increased body weight, liver weight, and amount of adipose tissues, especially in HFD-fed mice. Mechanistic studies revealed TiO2-NPs induced colonic mucus layer disruption and obesity-related microbiota dysbiosis. The damage on mucus was demonstrated through down-regulation of Muc2 gene and the absorption of mucin protein by TiO2-NPs. Consequently, mucus layer damage combined microbiota dysbiosis escalated the low-grade systemic inflammation, which exacerbated HFD-induced obesity. In contrast, gut microbiota depletion eliminated these effects, indicating gut microbiota were necessary for TiO2-NPs-induced inflammation and obesity. All the results stated the alarming role of TiO2-NPs in the HFD-driven obesity and emphasized the reevaluating the health impacts of nanoparticles commonly used in daily life, particularly, in susceptible population.

A Novel mRNA Signature Related to Immunity to Predict Survival and Immunotherapy Response in Hepatocellular Carcinoma

Background and Aims:Hepatocellular carcinoma(HCC)is the most common primary liver cancer and the incidence and mortality rates are increasing.Given the limited treatments of HCC and promising application of immunotherapy for cancer,we aimed to identify an immune-related prognostic signature that can predict overall survival(OS)rates and immunotherapy response in HCC.Methods:The initial signature development was conducted using a training dataset from the Cancer Genome Atlas followed by independent internal and external validations from that resource and the Gene Expression Omnibus.A signature based nomogram was generated using multivariate Cox regression analysis.The associations of signature score with tumor immune phenotype and response to immunotherapy were analyzed using single-sample gene set enrichment analysis and tumor immune dysfunction and exclusion algorithm.A cohort from Zhongshan Hospital was employed to verify the pre dictive robustness of the signature regarding prognostic risk and immunotherapy response.Results:The prognostic signature,IGS_(HCC),consisting of 22 immune-related genes,had independent prognostic ability,with training and validation cohorts.Also,IGS_(HCC)stratified HCC patients with different outcomes in subgroups.The prognostic accuracy of IGS_(HCC)was better than three reported prognostic signatures.The IGS_(HCC)-based nomogram had high accuracy and significant clinical benefits in predicting 3-and 5-year OS.IGS_(HCC)reflected distinct immunosuppressive phenotypes in low-and high-score groups.Patients with low IGS_(HCC)scores were more likely than those with high scores to benefit from immunotherapy.Conclusions:IGS_(HCC)predicted HCC prognosis and response to immunotherapy,and contributed to individualized clinical management.

Synergistic realization of high efficiency solar desalination and carbon dioxide reduction

Methods of seawater desalination and carbon dioxide(CO_(2))reduction using clean and renewable energy have attracted much attention withing the reducing fresh water and growing CO_(2)concentration.Here,we propose a synergistic method for solardriven desalination and CO_(2)reduction at the surface of sea using a three-dimensional titanium oxide-gold semiconductor/metal(TiO_(2)-Au NW/NPs(NW:nanowire,NP:nanoparticle))photothermal conversion membrane that can efficiently harvest a broad solar spectrum(200 to 2500 nm,94%)to undertake the conversion of light-to-heat and light-to-electricity.The TiO_(2)-Au NW/NPs membrane demonstrated a high solar vapor conversion efficiency of~90%,CO_(2)reduction yields of 0.066μmol·cm^(-2)CH_(4)and 0.015μmol·cm^(-2)CO within 5 h.In addition,the membrane efficiently evaporated seawater with different salt concentrations to produce drinking water which meet World Health Organization(WHO)and US Environmental Protection Agency(EPA)standards.This work provides an integrated solution for solar desalination and CO_(2)reduction at the surface of sea to reduce the harm to marine life caused by ocean acidification while producing pure water.